Sulfadimidine

MECHANISM OF ACTION

Sulfadimidine (Sulfamethazine) is a bacteriostatic sulfonamide antibiotic that works by inhibiting bacterial folic acid synthesis. It is a structural analog of para-aminobenzoic acid (PABA), a substrate required by bacteria to produce dihydrofolic acid via the enzyme dihydropteroate synthase. Sulfadimidine competitively inhibits this enzyme, preventing the formation of dihydrofolic acid, which is a precursor of tetrahydrofolic acid necessary for the synthesis of DNA, RNA, and proteins. As a result, bacterial growth and replication are halted, though the bacteria are not directly killed, making the drug bacteriostatic. Human cells are unaffected because they do not synthesize folic acid and instead obtain it from the diet, giving Sulfadimidine its selective action against bacteria.

PHARMACOKINETICS

Absorption

Sulfadimidine is efficiently and quickly absorbed from the gastrointestinal tract in monogastric animals such as humans, calves, and swine. Its absorption mainly occurs through passive diffusion, where the unionized form of the drug crosses the lipid membranes of the gut.

Distribution

The volume of distribution of Sulfadimidine is approximately 0.2–0.5 L/kg, indicating moderate distribution mainly into extracellular fluids. It penetrates well into most tissues and body fluids, including urine, bile, and milk, but has limited entry into the CSF under normal conditions.

Metabolism

Sulfadimidine is mainly metabolized in the liver, primarily through acetylation and, to a lesser extent, hydroxylation, producing metabolites such as the N4-acetyl derivative that are subsequently excreted via the kidneys. The rate of acetylation significantly affects its pharmacokinetics: fast acetylators display a biphasic plasma concentration-time curve, while slow acetylators exhibit a monophasic curve.

Excretion

Sulfadimidine is primarily excreted by the kidneys, both as unchanged drug and as metabolites, mainly the N4-acetyl derivative. Excretion occurs through glomerular filtration and tubular secretion, leading to high concentrations in the urine, which makes it effective for urinary tract infections. A smaller amount is also eliminated via bile, feces, and milk. Renal function and the animal’s acetylation rate can significantly influence the drug’s elimination and plasma levels.

PHARMACODYNAMICS

Sulfadimidine is a bacteriostatic sulfonamide that inhibits bacterial folic acid synthesis, preventing DNA, RNA, and protein production. It is broad-spectrum, targeting many Gram-positive and some Gram-negative bacteria, and its effectiveness depends on maintaining levels above the minimum inhibitory concentration (MIC). Human and animal cells are unaffected because they obtain folate from the diet.

ADMINISTRATION

Sulfadimidine can be administered via multiple routes, most commonly orally or by injection (intravenous, intramuscular, or subcutaneous), depending on the formulation and the species being treated. The choice of administration method differs between human and veterinary applications.

DOSAGE AND STRENGTH

Human Use (historical):

Oral tablets: 500 mg per dose

Typical adult dosage: 2–4 g per day, divided into 4 doses

Duration: Usually 7–10 days depending on infection type

Note: Sulfadimidine is rarely used in humans today.

Veterinary Use:

Oral powder for livestock/poultry: 33% Sulfadimidine

Injectable solution: 33–50 mg/mL, depending on species

Typical dosage:

Poultry: 25–50 mg/kg body weight per day

Pigs and calves: 25–30 mg/kg body weight per day

Duration: 3–5 days or as prescribed by a veterinarian

DRUG INTERACTIONS

Sulfadimidine can interact with several drugs, affecting their effectiveness or increasing side effects. It may enhance the anticoagulant effect of warfarin, increase methotrexate toxicity, or potentiate oral hypoglycemic agents, leading to hypoglycemia. Co-administration with other sulfonamides or diuretics can raise the risk of crystalluria or kidney damage, while combining with trimethoprim provides synergistic antibacterial effects but may increase the risk of bone marrow suppression. Additionally, Sulfadimidine can alter the renal excretion of other drugs, so caution is needed, especially in patients with renal or hepatic impairment.

FOOD INTERACTIONS

Sulfadimidine can interact with food in ways that may affect its absorption and efficacy. Foods that alter stomach pH, such as dairy products or antacids containing calcium or magnesium, can reduce the drug’s absorption. High-protein meals may also slightly delay absorption, though the effect is usually minor. To maximize effectiveness, Sulfadimidine is generally recommended to be taken on an empty stomach or with minimal food, unless otherwise directed by a veterinarian or physician.

CONTRAINDICATIONS

Sulfadimidine is contraindicated in individuals or animals with sulfonamide hypersensitivity, severe liver or kidney impairment, or certain blood disorders such as G6PD deficiency or porphyria. It should be avoided in pregnant or lactating females and neonates due to potential toxicity. Use is also not recommended in cases of dehydration or urinary obstruction, as this increases the risk of crystalluria and kidney damage.

SIDE EFFECTS

Common Side Effects:

• Nausea and vomiting

• Diarrhea and stomach pain

• Headache

• Rash and itching

• Loss of appetite

• Joint pain

• Increased sensitivity of the skin to sunlight (photosensitivity) 

Serious Side Effects:

• Severe allergic reactions.

• Severe skin reactions.

• Blood disorders.

• Kidney damage.

• Liver damage.

• Pseudomembranous colitis.

• Central nervous system effects.

OVERDOSE

Gastrointestinal issues: Nausea, vomiting, loss of appetite, stomach pain, colic.

Neurological effects: Dizziness, headache, drowsiness, mental depression, confusion, lack of muscle coordination (ataxia), muscle jerks and cramps, seizures, or even coma.

Kidney/Urinary problems: Hematuria (blood in urine), crystalluria (crystals in urine, which can lead to kidney stones and renal colic), anuria (absence of urine production), and general kidney damage.

Liver problems: Liver damage, hepatitis, jaundice (yellowing of skin or eyes).

Blood disorders (later manifestations): Anemia, agranulocytosis (low white blood cell count), thrombocytopenia (low platelet count), or other blood dyscrasias.

Other symptoms: Fever, unusual bleeding or bruising, sore throat, pale skin, weakness, fatigue, and general malaise.

TOXICITY

Sulfadimidine toxicity can result from overdose, prolonged use, or hypersensitivity, causing a range of symptoms from mild gastrointestinal upset and skin rashes to severe organ damage and potentially fatal blood disorders. A key concern, especially in animals, is crystalluria (formation of crystals in the urine) and subsequent kidney damage, particularly with dehydration or acidic urine.